We are investigating the influence of various aspects of cellular physiology on the establishment and maintenance of the interferon- induced antiviral state. We are attempting to identify and characterize the macromolecules made in response to interferon treatment. We have isolated a line of virus-resistant mutants of mouse embryo fibroblasts. These are being studied with respect to (a) the site of inhibition of virus replication, (b) the genetic properties of the virus-resistant phenotype and, (c) the possible involvement of the interferon system in the expression of the virus-resistant phenotype.